Homo sapiens
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PROVIDER: PRJNA94147 | ENA |
REPOSITORIES: ENA
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Project description:BAC CGH array profiling using Phi29-amplified microdissected samples
| PRJNA90451 | ENA
Project description:Details of the series are available in the publication Cardoso J. et al., “Chromosomal instability in MYH- and APC-mutant adenomatous polyps”, Cancer Research, accepted for publication. Abstract of the publication: “The vast majority of colorectal cancers display genetic instability, either in the chromosomal (CIN) or microsatellite (MIN) forms. While CIN tumors are per definition aneuploid, MIN colorectal cancers, caused by loss of mismatch repair function, are usually near-diploid. Recently, bi-allelic germline mutations in the MYH gene, were found to be responsible for MAP (MYH associated polyposis), an autosomal recessive predisposition to multiple colorectal polyps, often indistinguishable from the dominant FAP (familial adenomatous polyposis) syndrome caused by inherited APC mutations. Here, we analyzed MYH- and APC-mutant polyps by combining laser-capture microdissection, isothermal genomic DNA amplification, and array-CGH (comparative genomic hybridization). Smoothed quantile regression methods were applied to the MAP and FAP genomic profiles to discriminate chromosomes predominantly affected by gains and losses. Up to 80% of the MAP polyps showed aneuploid changes, which is significantly higher than the 60% found among FAP polyps. Both MAP and FAP adenomas were characterized by frequent losses at chromosome 1p, 17, 19 and 22, and gains affecting chromosome 7 and 13. The observation that aneuploidy is already detectable at early stages of MYH-driven tumorigenesis raises the possibility that CIN may contribute significantly to accelerated tumor progression, increased cancer risk, and poor prognosis in MAP.” Keywords: repeat, BAC, CGH
2005-12-25 | GSE3898 | GEO
Project description:Details of the series are available in the publication Cardoso J. et al., âChromosomal instability in MYH- and APC-mutant adenomatous polypsâ, Cancer Research, accepted for publication. Abstract of the publication: âThe vast majority of colorectal cancers display genetic instability, either in the chromosomal (CIN) or microsatellite (MIN) forms. While CIN tumors are per definition aneuploid, MIN colorectal cancers, caused by loss of mismatch repair function, are usually near-diploid. Recently, bi-allelic germline mutations in the MYH gene, were found to be responsible for MAP (MYH associated polyposis), an autosomal recessive predisposition to multiple colorectal polyps, often indistinguishable from the dominant FAP (familial adenomatous polyposis) syndrome caused by inherited APC mutations. Here, we analyzed MYH- and APC-mutant polyps by combining laser-capture microdissection, isothermal genomic DNA amplification, and array-CGH (comparative genomic hybridization). Smoothed quantile regression methods were applied to the MAP and FAP genomic profiles to discriminate chromosomes predominantly affected by gains and losses. Up to 80% of the MAP polyps showed aneuploid changes, which is significantly higher than the 60% found among FAP polyps. Both MAP and FAP adenomas were characterized by frequent losses at chromosome 1p, 17, 19 and 22, and gains affecting chromosome 7 and 13. The observation that aneuploidy is already detectable at early stages of MYH-driven tumorigenesis raises the possibility that CIN may contribute significantly to accelerated tumor progression, increased cancer risk, and poor prognosis in MAP.â Details of the series are available in the publication Cardoso J. et al., âChromosomal instability in MYH- and APC-mutant adenomatous polypsâ, Cancer Research, accepted for publication.
2010-06-30 | E-GEOD-3898 | biostudies-arrayexpress
Project description:Seventy blastomeres from fourteen frozen-thawed supernumerary human preimplantation embryos were disassociated and genomic was amplified using Multiple Displacement Amplification. BAC array-CGH was performed on the amplified products.
2012-10-15 | GSE34290 | GEO
Project description:Genomic changes in chromosome 8 are commonly observed in breast cancer cell lines and tumors. Fine mapping of such genomic changes, and evaluation of associated expression changes, are expected to provide reagents for diagnosis, insights into understanding the disease, and open up avenues for novel therapeutic intervention. We made an effort to search for genes on chromosome 8 with altered copy number and expression. A high resolution (0.1Mb) bacterial artificial chromosome (BAC) array of chromosome 8 that can detect single copy changes was developed using Phi29 DNA polymerase amplified BAC DNA. Hybridization of DNA from a breast cancer cell line (SKBR3) with two known amplified regions (8q21 and 8q24) resulted in resolving this region into 6 distinct amplicons, in addition identified 3 deleted regions. The boundaries and the peak of each region were verified by FISH, and the extent of amplification/deletion for each region was validated by qPCR. Using these BAC arrays, CGH was performed with a total of eight breast cancer cell lines, and common regions of genomic amplification/deletion were identified by segmentation analysis. Two consensus regions in 8q24 included a 1.2 Mb region (125.3-126.5 Mb) and a 1.0 Mb region (128.1-129.1 Mb) that were amplified in 7/8 cell lines, and in the 8q21 region there was a smaller 0.88 Mb region (86.62-87.50 Mb) amplified in 4/8 cell lines. A global expression analysis was performed for all these cell lines using a high-density oligonucleotide array to identify the genes whose expression correlated with amplification/deletion. Representative genes from 5 commonly amplified regions (REXO1L1, TMEM55A, TRMT12, MTSS1, EIF2C2, MYC) and 2 deleted regions (DPYSL2, NRG1 and NDRG1) were verified by qPCR and RT-qPCR for genomic and expression changes. Validation by RT-qPCR using RNA from 30 breast tumors showed that the TRMT12 (125.5 Mb) gene were overexpressed in many of the tumors. TRMT12 is homolog of a yeast gene encoding tRNA methyltransferase involved in biosythesis of a modified base in a tRNA. It would be interesting to explore the role of TRMT12 and the RNA processing pathway in tumorigenesis. Keywords: Comparative Genomic Hybridization (CGH), Breast cancer cell lines, Expression, BAC array, Oligo expression array
2007-05-07 | GSE6567 | GEO
Project description:Seventy blastomeres from fourteen frozen-thawed supernumerary human preimplantation embryos were disassociated and genomic was amplified using Multiple Displacement Amplification. BAC array-CGH was performed on the amplified products. BAC array-CGH on single blastomeres amplified by Multiple Displacement Amplification.
2012-10-15 | E-GEOD-34290 | biostudies-arrayexpress
Project description:Expression profiling is a well established tool for the genome-wide analysis of the transcriptional activity of human neoplasia. However, the high sensitivity of this approach combined with the well-known cellular and molecular heterogeneity of cancer often result in extremely complex and extended expression signatures of difficult functional interpretation. The majority of sporadic colorectal cancer cases are triggered by mutations in the APC tumor suppressor gene leading to constitutive activation of the Wnt/b-catenin signaling pathway and adenoma formation. Notwithstanding this common genetic basis, colorectal cancers are very heterogeneous in their degree of differentiation, growth rate and malignant potential. Here, we applied cross-species comparison of expression profiles of intestinal polyps derived from hereditary colorectal cancer patients carrying APC germline mutations, and from a mouse model carrying a targeted inactivating mutation in the mouse homologue Apc. This comparative approach resulted in the establishment of a conserved signature encompassing 166 genes differentially expressed between adenomas and normal intestinal mucosa in both species. Functional analysis of the conserved genes revealed a general increase in cell proliferation and the activation of the Wnt/b-catenin signal transduction pathway, as expected from the selection of APC/Apc-mutant intestinal adenomas. Moreover, the conserved signature is able to resolve expression profiles from hereditary polyposis patients carrying APC germline mutations from those with bi-allelic incativation of the MYH gene. Keywords: normal versus tumor comparison; compare expression profiles from microdissected samples with distinct germline mutations (FAP vs. MAP).
2008-04-01 | GSE9689 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE4078: Phi29-based amplification of fresh-frozen and FFPE tumor DNA GSE4079: Genome-Wide Gene Dosage Representation in Phi29-Amplified DNA Abstract: Sufficient quantity of genomic DNA can be a bottleneck in genome-wide analysis of clinical tissue samples. DNA polymerase Phi29 can be used for the random-primed amplification of whole genomes, although the amplification may introduce bias in gene dosage. We have performed a detailed investigation of this technique in archival fresh-frozen and formalin-fixed/paraffin-embedded tumor DNA by using cDNA microarray-based comparative genomic hybridization. Phi29 amplified DNA from matched pairs of fresh-frozen and formalin-fixed/paraffin-embedded tumor samples with similar efficiency. The distortion in gene dosage representation in the amplified DNA was nonrandom and reproducibly involved distinct genomic loci. Regional amplification efficiency was significantly linked to regional GC content of the template genome. The biased gene representation in amplified tumor DNA could be effectively normalized by using amplified reference DNA. Our data suggest that genome-wide gene dosage alterations in clinical tumor samples can be reliably assessed from a few hundred tumor cells. Therefore, this amplification method should lend itself to high-throughput genetic analyses of limited sources of tumor, such as fine-needle biopsies, laser-microdissected tissue, and small paraffin-embedded specimens. Refer to individual Series
2006-03-14 | E-GEOD-4467 | biostudies-arrayexpress
Project description:Expression profiling is a well established tool for the genome-wide analysis of the transcriptional activity of human neoplasia. However, the high sensitivity of this approach combined with the well-known cellular and molecular heterogeneity of cancer often result in extremely complex and extended expression signatures of difficult functional interpretation. The majority of sporadic colorectal cancer cases are triggered by mutations in the APC tumor suppressor gene leading to constitutive activation of the Wnt/b-catenin signaling pathway and adenoma formation. Notwithstanding this common genetic basis, colorectal cancers are very heterogeneous in their degree of differentiation, growth rate and malignant potential. Here, we applied cross-species comparison of expression profiles of intestinal polyps derived from hereditary colorectal cancer patients carrying APC germline mutations, and from a mouse model carrying a targeted inactivating mutation in the mouse homologue Apc. This comparative approach resulted in the establishment of a conserved signature encompassing 166 genes differentially expressed between adenomas and normal intestinal mucosa in both species. Functional analysis of the conserved genes revealed a general increase in cell proliferation and the activation of the Wnt/b-catenin signal transduction pathway, as expected from the selection of APC/Apc-mutant intestinal adenomas. Moreover, the conserved signature is able to resolve expression profiles from hereditary polyposis patients carrying APC germline mutations from those with bi-allelic incativation of the MYH gene. Keywords: normal versus tumor comparison; compare expression profiles from microdissected samples with distinct germline mutations (FAP vs. MAP). Here, we report the expression profiles from normal and intestinal adenomatous tissue from FAP (familial adenomatous polyposis) and MAP (MUTY-associated polyposis) patients with established APC and MUTY germline mutations. Total RNA samples were obtianed by laser capture microdissection.
2008-04-01 | E-GEOD-9689 | biostudies-arrayexpress
Project description:Abstract: Sufficient quantity of genomic DNA can be a bottleneck in genome-wide analysis of clinical tissue samples. DNA polymerase Phi29 can be used for the random-primed amplification of whole genomes, although the amplification may introduce bias in gene dosage. We have performed a detailed investigation of this technique in archival fresh-frozen and formalin-fixed/paraffin-embedded tumor DNA by using cDNA microarray-based comparative genomic hybridization. Phi29 amplified DNA from matched pairs of fresh-frozen and formalin-fixed/paraffin-embedded tumor samples with similar efficiency. The distortion in gene dosage representation in the amplified DNA was nonrandom and reproducibly involved distinct genomic loci. Regional amplification efficiency was significantly linked to regional GC content of the template genome. The biased gene representation in amplified tumor DNA could be effectively normalized by using amplified reference DNA. Our data suggest that genome-wide gene dosage alterations in clinical tumor samples can be reliably assessed from a few hundred tumor cells. Therefore, this amplification method should lend itself to high-throughput genetic analyses of limited sources of tumor, such as fine-needle biopsies, laser-microdissected tissue, and small paraffin-embedded specimens. This SuperSeries is composed of the SubSeries listed below.
2006-03-15 | GSE4467 | GEO